An Empirical Study of Amide-Heteroarene π-Stacking Interactions Using Reversible Inhibitors of a Bacterial Serine Hydrolase.

ABSTRACT: Compared to aryl-aryl π-stacking interactions, the analogous stacking of heteroarenes on amide π systems is less well understood and vastly underutilized in structure-based drug design. Recent theoretical studies have delineated the important geometric coordinates of the interaction, some of which have been confirmed with synthetic model systems based on Rebek imides. Unfortunately, a broadly useful and tractable protein-ligand model system of this interaction has remained elusive. Here we employed a known inhibitor scaffold to study π-stacking of diverse heteroarene substituents on the amide face of Gly238 in the cephalosporinases CTX-M-14 and CTX-M-27. Biochemical inhibition constants (K _i) and biophysical binding constants (K _d) were determined for ni

SUBMITTER: DeFrees K 

PROVIDER: S-EPMC7410147 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature